Good afternoon. Welcome to day two of the Barclays Global Healthcare Conference. My name is Carter Gould, Senior Biopharma Analyst here at Barclays, and I am pleased to welcome Merck to the stage. Merck has been one of our top-ranked names for a bit here and certainly keep coming off a pretty stellar 2022. Follow that up with a solid start to 2023 with PAH data, which we're going to touch on. Joining us from the company, President of Merck Human Health, Jannie Oosthuizen, as well as Peter Dannenbaum from the IR team. Peter, Jannie, thank you very much for joining us today.
Well, thank you for having us.
We can hop into Q&A unless you wanted to make any opening comments?
No, I was actually gonna say, you know, Merck is coming off a great 2022, but you said that. We had a really exciting start with some of the data releases and KEYNOTE-091 launch. I'm sure that's material for a good discussion now.
Absolutely
L ooking forward to talk to you.
Right. We just spent time, I think about 10 days ago now. maybe not even.
Yeah
I think we're around 10 days, since we were in New Orleans there, on the back of the sotatercept phase III data. I guess I'll open it up with a relatively broad question, which is, when we think about sotatercept's potential integration into the treatment paradigm in PAH, how do you see that playing out on the back of this initial data?
Yeah, as you said, it's really been, you know, a very, very strong data set we were able to communicate at the conclusion of the STELLAR trial. We believe that based on the data that sotatercept will change the way that PAH is treated. Our aspiration is that sotatercept will become a foundational treatment in PAH. As we know, you know, this is a very specialized treatment community. PAH experts, mostly pulmonologists and cardiologists with a key interest in this disease. Treating most of these patients in a highly specialized treatment centers. There's about 150 of these throughout the country. I think the feedback we're hearing is really positive in terms of the scientific leaders, but increasingly the broader treatment community.
We think we're gonna see really strong uptake of sotatercept as a treatment in the space as we move forward. You know, there's more to learn over the next few weeks in terms of just how physicians are thinking in terms of where to use it. This is a population in STELLAR that is very similar to what you find out in the market. These patients have been diagnosed for eight to nine years in the trial. They've been, maybe 40% on a doublet, 60% on triple therapy, so highly treated patients. We think it's gonna be, you know, very much an applicable data set as physicians think of the existing patients that sit out in the market.
I think it's gonna be interesting to see how they think about how soon to introduce sotatercept, with, for these patients.
When we think about, like, what part of that population is gonna be dynamic versus a patient who may be a little bit closer to stable. Do PAH docs think about it like that, or is it just gonna be, "Hey, this is a new foundational treatment, and you're clearly seeing gains, so.
Yeah.
Y ou should adopt it"?
Yeah. I think, you know. STELLAR is obviously one data set. We've got another trial, HYPERION.
Yeah.
I think that is really answering the question, how soon after diagnosis should you introduce sotatercept? We've heard some physicians saying that as soon as, you know, the patient is stable on a doublet vasorelaxers, they will think of introducing sotatercept. I think the trial is really gonna help us to figure that out. Then obviously the STELLAR population is continuing in Soteria, there's also gonna be an opportunity to continue to see how they do.
Okay. While the hazard ratio was outstanding, there was a bleeding risk associated with the drug. Let's start off at a high level. Can you talk about that bleeding risk and how you think that may or may not impact?
Right
C ommercial adoption?
The epistaxis bleeding that we saw in the trial were mostly gum, and nose bleeds. They were mild. You know, there were no discontinuations as a result of that. I think the additional good news is that none of that were gastrointestinal or intracranial bleeds.
Got it.
It was mild, it was manageable, and didn't lead to any discontinuation.
Okay. On that point, I just. There were no GI bleeds?
No, no GI.
Okay. When you think about just the uncertainty that these, maybe, comes to mind in these docs, just the uncertainty around bleeds, is that gonna have an impact in any way you think?
Yeah. I think, you know, in general in PAH, you know, side effects is something that physicians think about a lot in terms of the currently available treatments. I think when there's known side effects like this, you know, everybody's gonna be thinking about it. I think the, you know, the efficacy signal was so strong that we believe the benefit risk profile is really strong in favor of sotatercept. Then as I said with SOTERIA, we're gonna be able to continue to monitor.
Right.
You know, there's been some other side effects that will receive the same attention, so nobody's dismissing it. I think today we feel really good about the benefit risk profile and the fact that we have opportunity to continue to monitor how this is continuing to play out.
Okay. When we think about the go-to-market strategy here, is this gonna require an additional sales force above and beyond kind of what's already being used for your existing for VERQUVO or the, you know, Adempas?
We, you know, we obviously have a legacy in cardiovascular with some current heart failure products in the market in the U.S. This is a slightly different treatment population. You know, it's really focused on PAH. As I said, it's a fairly tight, small community. Most patients are sitting in these 150 centers in the U.S. Our commitment is to really stand up a world-class rare disease operating model that can cater for, you know, this treatment community and the stakeholders involved in PAH. That's in the U.S. It's gonna be, you know, I think a very efficient sales force that we will put out, and we're gonna highly augment it with some of our digital capabilities in terms of reaching, you know, this community also through different channels.
And, you know, leveraging just how connected this community is in terms of scientific leaders, understanding of the data, a gaining interest in this area and every development that happens. If you want outside the U.S., you know, we have an, you know, the product in collaboration with Bayer that we can leverage. In Europe, there's about 115 of these centers. Again, really concentrated, 45 of them in Germany and about 20-25 in France. We think we can have a significant base of reach through these highly concentrated engagement.
Okay. Maybe one last point on sotatercept, and that is, I think it's lost on some people that you do have CADENCE data not too far on the horizon. What success in left heart disease might, you know, do for an asset like sotatercept and just.
Yeah.
What that might mean commercially.
Yeah, that's right. I mean, as we look at, you know, this exciting data in pulmonary arterial hypertension associated with the right heart, the question is, you know, when you look at the unloading that, sotatercept bring on the right heart that we see through huge reduction in or NT-proBNP, you know, what could that mean for pulmonary hypertension associated with left heart, disease? You know, that's an area where there's really nothing for these patients today. A huge unmet need. Even diagnosis is low, you know, so we believe this could be a meaningful opportunity, where we can make a significant difference for these patients, but really add a significant opportunity to sotatercept overall.
Just thinking about patient numbers, can you help give us some context, left heart.
Yeah. I mean, right now the EP is really low because there's really nothing. There's very poor diagnosis. We know this exists. This is work as CADENCE plays out that we will continue to do to really inform ourselves how big this could be.
Okay. Perfect. let's go to the other kind of darling of ACC. That was the PCSK9 data. Merck has kind of framed this really about democratizing PCSK9 access with an oral. What gives you, I guess, confidence that this is really a, you know, an oral slash access issue and not a larger issue of just patient inertia around a generally asymptomatic disease?
I think starting with the last one, we know that there's really broad high volume statin use already for a lot of these patients, right? Even though it's asymptomatic, there is a sense of urgency to treat, and a lot of patients are attempting to get their LDL cholesterol to a reasonable target. We know it's really difficult to get these patients to target, right? If you start with just the unmet need, we know about 85% of cardiovascular disease results from ASCVD. That is out there. Despite that, only 5% of patients today, or let me rather start with only 70% or, you know, only 70% of patients are managed to goal, right?
We know that with statins it's really difficult to get patients to the right dose, to keep them on the right dose and really bring those lipid levels down. Today, only about 5% of patients are accessing an injectable PCSK9. When you look at all this, there's no doubt a significant opportunity, significant unmet need. We know part of the issue with injectable PCSK9 is clearly, you know, the payer restrictions due to where to start it from a price perspective, how it's being managed. It's also the setting where patients need to access this.
If we bring that, you know, into then offering a solution in a tablet where we can really look at a price point and looking at innovative payer agreements where we can open access from a payer perspective and make this available in a primary care setting where patients can get this from their primary care physician, we believe that we can make a very meaningful difference and really broaden access, not just in the U.S. but also outside of the U.S.
Do you think you can see that meaningful adoption even ahead of formal CV data?
Yeah. I mean, CV data will always help, and we will pursue that, as you know. We believe there's a meaningful opportunity. I mean, if you just look at the secondary prevention market, it's 40 million patients around the world where there's a higher sense of urgency. We think there will also be a reference to some of the existing outcome data that could help. You know, we think we can pursue a meaningful opportunity. We obviously need to open up payer access that we just talked about. We will pursue innovative ways of creating that. That will help with guideline updates, that will help with policy shifts.
I think it's really creating all these positive aspects, including ultimately, outcome data that will further expand access, especially in some of the more restricted markets.
Okay. I think the number one negative pushback to PCSK9 data was the full effects and to what extent you think that's gonna limit adoption. I guess the eight-hour fasting ahead of time, I guess, on some level, that was something you had probably didn't make. It wasn't probably gonna be that big of a hindrance if people are taking it right in the morning, but maybe there's some nuance I'm missing and you think about how that's gonna impact the commercial adoption.
Yeah, that's right. I think, you know, a lot of patients that take their chronic medication is used to taking it in the morning. That would probably be, you know, the right thing to advise patients of. Then a 30-minute wait before food intake, which is very similar to what the statins have to do today. We don't see that as a barrier. I think it's very easy for patients to incorporate that approach into their daily life.
Okay. Maybe just to wrap up on the CV portfolio. Now you've got good momentum on the back of sotatercept and PCSK9. Can you maybe help. You know, you have some other additional assets beyond that, but just that momentum and kinda getting those foundational kind of linchpins to the franchise, what that. How that, you know, sets you up for the broader franchise and drives, you know, synergies across the entire CV org.
Yeah. I mean, you know, from a CV perspective, we have some others. We also have a, you know, edible HTC, right? That will come into PAH. Certainly we will continue to build in this space. I also think we will continue to be, in a way, agnostic to therapeutic area. You know, I think Merck's approach have always been to pursue the best science, really look at unmet patient need. Clearly, you know, we wanted to have a fit with some of our internal capabilities because that makes us the advantage owner of everything that we bring in, and we can really develop for a differentiated patient impact ultimately, that really drives some long-term value. You know, we've done some of that recently.
You've seen the collaboration with Kelun-Biotech on some of the ADCs, the recent agreement with Moderna on the personalized cancer vaccine. We see this, you know, in terms of other areas that we will continue to pursue. No doubt, you know, these internal capabilities, coupled with the scientific, you know, developments that happens outside of Merck's walls, is something that we see as beneficial in how we approach this development.
Okay. Maybe ask an initial question on just sort of business development. How does that success within a portfolio then, you know, potentially then drive, you know, additional focus in BE within CV now that you have that kind of, that foothold in the space? Does Merck think about it like that in terms of, like, that portfolio approach, or is it more agnostic?
I think it is more agnostic.
Okay.
I mean, again, certainly, you know, once you have a presence, it help if you build it out. You know, we've seen that in oncology over the last few years. You know, we have never restricted ourselves to just stay within those areas. I think the key is about identify cutting-edge science, couple it with capability to assess and decide, can we do something differentiated with this? We've also continued to build capability, right? If you look at immunology, we've brought in a lot of external capability. We've learned a lot from immuno-oncology that we apply into immunology, so it's also dynamic in a way. I think it benefits us to have an agnostic approach to this.
Okay. Maybe to bring Peter in here real quick. Just if you could outline kind of what you guys have framed in terms of how big you think CV could be and over kind of what time frame?
A year ago, we hosted a deep dive event focused on our cardiovascular pipeline. Since that time, obviously, based on the discussions, some positive things have happened. At that time, we had said, on a non-adjusted basis, we saw greater than $10 billion of commercial revenue potential by the mid-2030s. As we've had some de-risking events, we've now been saying we have even greater confidence that that can occur.
Okay. We're 15 minutes into the presentation. We have not said the KEYTRUDA word at all, which I don't think would have happened anytime in the prior five years. Maybe let's talk about some of the drivers on KEYTRUDA. 2022 was a solid year for KEYTRUDA on the back of the number of label extensions. As we think about 2023, are those drivers still gonna be meaningful as even if sort of their those approvals kind of anniversary?
Yeah, I think, exactly. I mean, we continue to hold a very strong leadership position at IO, you know, and continue to increase share, new patient as well as overall class share. I think there's a really strong foundation. We continue to see good momentum growth across, you know, almost all of the tumor types. Certainly holding a very strong position in lung, which is significant portion of KEYTRUDA, but also very meaningful expansion into the earliest stage cancers like them. Really what we saw in 2022 was triple-negative breast adjuvant Oh, new adjuvant triple-negative breast, adjuvant melanoma, adjuvant RCC driving significant growth, and a lot of that is continuing, you know, in 2023.
Obviously, you know, we continue to go further in terms of KEYNOTE-921. We've got PEARLS on KEYNOTE-671. The early-stage indications is gonna continue to be a strong driver of growth. We expect that it will be about 30% of our growth between now and 2025. Early stages would make up about 25% of KEYTRUDA revenue by 2027. I think we're in a, in a good place in terms of the drivers playing out.
I wanna come back to the 091 data. Pretty sure it was me who asked the question on the call, and I think Rob tried to level set expectations in terms of adoption based on the 091 data. You followed it up with 671 data that came way ahead of expectations, and now you got, you know, all through to date. Does that then potentially accelerate that adoption? Should we be thinking about that on a faster scale than maybe kind of how we're framing KEYTRUDA?
I think there's two things. I think the data, you know, there's no issue with the data. We feel very strong about, you know, in KEYNOTE-921, pursuing stage I-B, II, and III-A. With KEYNOTE-671, it's stage II, III-A, and III-B, right? Some of that. The data, you know, no question about the data. I think what Rob was trying to get across is that, you know, if you look at two significant tumor areas like lung and triple-negative breast, so lung and breast, almost equal in terms of the number of patients. You know, but in breast, we see a high level of screening, we see a high level of diagnosis, we see a high level of treatment, pre and post-surgery, right?
Because most of those patients are young, you know, they're healthy, and they get this. Whereas in lung cancer, what we see is really low screening rates in the U.S., around 6%. Only about 44% of patients are diagnosed. What we also see is that a significant number of patients are not eligible for surgery, right. You have a little bit of a different drop-off in the early-stage lung setting that is very different from breast. From that perspective, you know, we will see an uptake, but it's probably not gonna be as we saw it in.
Okay. That's good context. Maybe moving subcutaneous KEYTRUDA. For the person running the commercial franchise, this is tremendous opportunity, but also a number of kind of issues to kinda potentially navigate here. Maybe help first off frame how you believe patients and clinicians will think about subcutaneous KEYTRUDA in a world in which we have biosimilar IV. Well, maybe start there.
First of all, I mean, we continue to drive these innovations to make a significant difference in terms of patient outcomes, whether it's, you know, higher efficacy, in this case, much, much greater convenience, right? That's really why we continue to innovate in this form. KEYTRUDA subcutaneous certainly will be a big time saver in terms of how patients get their drug administered. The way we think about it is that, you know, if you think of the early stage where patients are typically on longer treatment cycles, and it might be, you know, in most of the adjuvant settings, KEYTRUDA only subcutaneous will be a very convenient way to deliver KEYTRUDA, both for the patient as well as for the offices where it gets administered, right?
It's a very different logistical setup, and it saves a lot of time and provides for efficiency. The other places where KEYTRUDA is used on its own, this is a place where you know, subcutaneous could easily slot in, as well as in combination with oral treatments, so lentiginous melanomas. So that is, you know, roughly it's gonna be by 2028, about 50% of where the KEYTRUDA volume sit is in a space where the subcutaneous KEYTRUDA can bring a lot of patient convenience as well as efficiency for the practices where it's being administered.
Okay. When, you know, the added wrinkle here is IRA impact-
Yeah.
How that, you know, sort of when would the clock start for subcutaneous KEYTRUDA?
That is a big question. I mean, you know, one of the things with the IRA, we don't know exactly how they will look at these different formulations. This will be a unique co-formulation, right? From that perspective, it will be unique, it will be novel, it will bring significant treatment and patient value. You know, we are looking closely at how we think the IRA is gonna treat these. You know, that's something we will hopefully get increasingly more clarity on as we work with CMS on rules and execution, implementation of how the negotiations ultimately will happen.
Okay. Maybe for Peter here, just how we think about the two formulations, and you talked about prioritizing the second formulation. Kinda what happens with the first formulation? Is that still potentially coming to market, or just sort of?
Yeah. The phase III and the fir, and the initial.
Yeah.
Subcutaneous program will read out this year. It'll help inform our broader efforts with subQ. We've said that we are likely to prioritize the second program, which is in combination with hyaluronidase, in part because of the efficiency with which it delivers the drug into the body, fewer injections, site reactions, and the ability to potentially dose every six weeks. When you're thinking about early-stage patients, that's a real benefit.
Right.
Jannie mentioned convenience, but it's really, like you say, it's an access issue for many of these patients, particularly in early stage or for patients that live far away from in infusion centers, to be able to access at their local physician's office.
Okay, coming back to lung for a second, the focus on TIGIT. We had Gilead here earlier. We had Roche yesterday, as I recall. You know, just given KEYTRUDA's strong position in lung today, when you think about what it would take to really move the needle in first-line lung, how do you think about that? It seems on some level it would take a pretty overwhelming kind of hazard ratio or survival benefit to kind of move the needle.
Yeah.
You also have your own program.
Yeah.
Kinda how you think about the balance there and the competitive threats.
Well, first of all, I think when we move the needle in that setting, which will be great news for patients, right? That's why I think we will continue to try and do that because a lot of patients are benefiting. We never forget that there are still patients who are not benefiting from current standard of care. That will be a good thing the day when it happens. We hope it could be us. You know, in terms of our TIGIT program within our KeyVibe program, we have 9 trials ongoing, of which five are in phase III right now, three in non-small cell, one in small cell, and recently announced the adjuvant study in melanoma.
You know, obviously, we don't compare head-to-head on the TIGIT assets. We do believe we have an asset that is very clean, you know, high affinity for where it binds. It has performed well in the models and in human cells. We also have the opportunity to obviously combine it with KEYTRUDA, right? Which others are not able to do. We hope that, you know, we can show a differentiated effect. The data will inform us. We continue to look at, you know, not just what's happening within our own set of studies and data sets, but also what's happening externally to better inform where we go next and how do we continue to develop this co-formulation.
Okay.
As you know, we have a strong position in lung based on really strong overall survival results in a variety of different settings in lung. Whether it's us or competitors, you need to show meaningful benefit over what's already been achieved with KEYTRUDA.
I don't have time to ask the deeper DE question. Now that we know that melanoma data with Moderna is gonna be at AACR, can you maybe just kinda help frame, you know, the path forward there? There's been a lot of talk about potentially filing on that data. Just the latest from Roche.
Yes. We look forward to Moderna's presentation of that data. It's very exciting. We've seen strong top line release. We have always said it's a, you know, a relatively small phase II trial in a novel setting. We look forward to proceeding as quickly as we can into phase III. We'll have to see how those discussions with the regulators turn out. We always are open to the idea of filing on phase II. We're looking forward to the phase III trial.
All right. Fair enough. We're out of time.
All right.
Jannie, Peter, thank you very much for the time.
Thanks so much, Carter.
Great. Thank you, Carter.